Effect of rifampicin on Toll-like receptor system gene expression in brain structures of rats with prenatal alcohol exposure

Alcohol intake during pregnancy may affect the normal course of fetal development, causing the symptoms of fetal alcohol spectrum disorders (FASD). There is evidence that a number of prenatal pathologic conditions exhibit altered expression of several pro- and anti-inflammatory cytokines. In our study, we focused on studying expression of numerous pro- and anti-inflammatory cytokine genes in the forebrain and temporal regions of rat brain during the postnatal development, thus modeling prenatal alcohol exposure effects (PAE). We also evaluated expression of genes associated with regulation of genes controlling expression of pro- and anti-inflammatory cytokines. Moreover, the objectives of our study included pharmacological correction of the observed changes by rifampicin (Rif), a potential pharmacological agent which had a neuroprotective effect shown by other studies,. The experimental model of PAE was produced by oral intake of 15% ethanol solution to pregnant female rats throughout pregnancy. The drug injections were performed to the pups from the 1 to the 7 postnatal days. Brain structures were sampled for gene expression analysis on the 8 postnatal day. The results of the study showed distinct changes in Tlr3 and Tlr4 gene expression in anterior and temporal lobes of brain on the 8 day of postnatal development. Expression of Myd88 and Ticam genes showed multidirectional changes among the studied brain structures of PAE rats. The increased mRNA level of proinflammatory genes was noted. Usage of Rif in experiments showed the ability of Rif (50 mg/kg) to correct the observed long-term pathological changes in the expression of the genes under study. It is of interest to study the dose-dependent effect in the future, as well as to investigate the revealed changes at the level of protein analysis. In future studies, it seems important to evaluate TLR signaling system in other brain structures with PAE, as well as at different terms of postnatal development in ontogenesis.

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